DESCRIPTION: Although the inability to develop normal social attachments is characteristic of many human psychopathologies including autism and schizophrenia, surprisingly little is known about the neurological basis of social bond formation. Despite differences in the complexity and ultimate function of attachments in human and non-human species, the formation of all social relationships is dependent on the fundamental ability of an organism to discriminate between novel and familiar individuals. For more than three decades, Oxytocin (OT) has been linked to cognitive and behavioral processes related to both memory and attachment, and has long been considered an attractive candidate in the mediation of individual recognition. The recent development of an OT null mutation mouse (OT-KO) has provided an important and novel tool in the investigation of the neural basis of social attachment and has made it possible to establish the necessity of OT in the development of social memories. The work described in this proposal will further develop this OT-KO model of deficits in individual recognition in an effort to elucidate the neural mechanisms underlying the formation of social attachments. Specifically, the proposal will address the anatomical circuits involved in the discrimination of novel and familiar individuals and the neural mechanisms through which oxytocin is able to affect social recognition. Brain activation patterns after brief social interactions, lesions, and site-specific injections of the OT peptide and its antagonist will help to define the neuroanatomical circuit necessary for the recognition of familiar individuals. Pharmacological manipulations in both OT-KO and WT mice will reveal functional interactions between OT and the forebrain monoaminergic systems important to social recognition.